Over the last decades, health researchers and professionals have been searching for a material that may be applied as an alloplastic graft which, as well as integrating with the tissue to be replaced, may also induce regeneration of the damaged tissue and be reabsorbed at the same rate in which the new tissue is formed, these materials being recently classified as third generation biomaterials.
Ceramic materials have been performing well in this field of biological application and are widely studied due to high biocompatibility and osteoconductive properties.
Currently, there is a wide variety of vitreous material or bioactive or biocompatible ceramics, such as dental ceramics, granular or scaffold-shaped bone grafts for bone replacement, etc. Its clinical applications include repair of hard tissue such as bones, teeth, and eventually soft tissue, see Hench, L. L; Wilson, J. An Introduction to Bioceramics. Advanced Series in Ceramics. Singapore: World Scientific Publishing Ltd., 993.
Among the most commonly used materials for the aforementioned applications, bioactive glasses have become increasingly requested due to higher bioactivity and, therefore, advantageous when compared to other materials applied as synthetic grafts (also known as alloplastic grafts).
These glasses are part of a class of biomaterials based on vitreous silicate compounds, according to the article by Cerruti, M. G. et al. An analytical model for the dissolution of different particle size samples of Bioglass in TRIS-buffered solution. Biomaterials, v. 26, p. 4903-4911, 2005, which have excellent bioactive and osteoconductive properties; see related article by Oonishi et al., Particulate bioglass compared with hydroxyapatite as a bone graft substitute. Clin Orthop Relat Res, p. 316-325, 1997. They were developed by Hench, L. L. and collaborators in the early 1970s, according to the quote above and, ever since, the behavior of these materials and the many possible bioactive compositions are studied.
However, for in vivo applications, this material has been limited only to small monolithic parts, to particulate and granules or rigid scaffolds, which prevent its application in all clinical cases, since the choice of the bone grafting to be used depends on many factors such as size of the defect, number of surrounding walls, etc. This happens because the vast majority of bioactive vitreous compositions developed thus far have a high crystallization tendency, and thus, a thermal treatment process is not feasible. Therefore, the development of new vitreous compositions capable of withstanding heating/cooling treatments without loss of vitreous phase and bioactive characteristics is extremely recent and important.
With these different processes, it is possible to obtain fibers that may lead to bioactive meshes, fabrics, scaffolds or curatives. This also represents a very promising advancement for alloplastic materials, as it further broadens the range of utilization of bioactive glasses and enables its use in cases when one or more types of osteoconductive and/or osteoinductive materials are needed.
The development of fibers and fabrics from this type of biomaterial would enable the creation of grafts extremely reactive to body fluids, of easier handling, adjustable to the bone cavity and with good mechanical properties.
Bioactive glasses may feature a very broad field of application when presented as fibers, meshes and fabrics. This type of conformity may find its main use as a synthetic graft (alloplastic), acting as a guide for the new formation of soft and/or hard tissue.
In dentistry, for example, these vitreous fiber meshes or fabrics may be used as reinforcements in periodontal surgery, surgical procedures for increase of bone volume of the alveolar ridge for periodontal surgery, surgical procedures for increase of bone volume of the alveolar ridge to enable rehabilitation with implants, maxillary sinus augmentation, etc.; and in medicine these fabrics could be used in general orthopedic surgery, fractures, craniofacial deformities and general soft tissue regeneration.
The bioactive glass fiber fabrics and meshes may also be able to replace titanium meshes (FIG. 1), which are widely used nowadays in fracture surgery which involve orbital floor (blow-out eye region fractures), see Pinto, J. G. S. et al. Enxerto autógeno x biomateriais no tratamento de fraturas e deformidades faciais-uma revisão de conceitos atuais. RFO, v. 12, p. 79-84, 2007, and also associated to particulate autogenous bone grafts or allografts for maintenance and stabilization in the desired location, as mentioned in Cortez, A. L. V. et al., Reconstrução de Maxila Atrófica utilizando Osso Autogéneo e Malha de Titânio para Posterior Reabilitação com Implantes-Caso Clinico. Revista Portuguesa de Estomatologia, Medicina Dentária e Cirurgia Maxilofacial, v. 45, p. 163-167, 2004.
Other recently discovered fields of application for bioactive fibers are: use in dermatological wounds and ulcerations, such as varicose ulcers and/or skin wounds due to chronic diseases, such as diabetes, which take long periods to heal or even are unable to fully heal on its own.
However, the majority of bioactive glass compositions developed thus far feature a high crystallization tendency and a very limited working range, according to U.S. Pat. No. 6,054,400, since it normally has great amounts of alkaline and alkaline earth (R). These elements are considered structure modifiers, as they create non-bridging oxygens (—Si—O—R) and smaller structural units; this causes vitreous compositions to be more susceptible to crystallization, since the energy released by the heating during the fiber manufacturing processes is enough to cause rupture of chemical bonds, which are weaker than bridging Si—O—Si bonds, thus enabling atom rearrangement and subsequent devitrification, see Arstila, H. et al. Factors affecting crystallization of bioactive glasses. Journal of the European Ceramic Society, v. 27, p. 1543-1546, 2007.
Another behavior of this type of vitreous formulation, which tends to affect the fabrication of fibers, is a viscous behavior characterized by rapid change with little temperature variations, that is, these glasses are known as “fragile” glass compositions, as mentioned in the article by Arstla, H. et al., above.
Therefore, these materials in general cannot be manufactured via conventional methods, such as the downdrawing process, and for this reason, the fibers obtained with traditional bioactive vitreous compositions are currently made mostly through the melt spinning process. Nevertheless, this technique is only capable of producing small fibers or extremely thin strip-shaped samples, see /Melt_spinning; http://en.wikipedia.org/wiki.
The vitreous compositions most commonly known for obtaining fibers through this process are: 13-93 and 9-93 glasses, and this is possible because both formulations have a significantly higher amount of silica in relation to standard bioactive vitreous compositions, with 53 wt % and 54 wt %, respectively; while the Bioglass® 45S5 has approximately 45 wt %, as mentioned in the articles by Pirhonen, E. et al. Manufacturing, Mechanical Characterization, and In vitro Performance of Bioactive Glass 13-93 Fibers. Wiley InterScience, 2005. IOD: 10.1002/jbm.b.30429 and Pirhonen, E, et al. Mechanical Properties of Bioactive Glass 9-93 Fibers. Acta Biomaterial, v. 2, p. 103-107, 2006.
This represents a major stability gain regarding the crystallization phenomenon, since silica is considered a glass former element. However, this broader working range of the bioactive 13-93 glass that allows creation of fibers leads to a kinetic of slower superficial reactions than the Bioglass 45S5. This glass takes approximately seven days in a SBF-K9 solution for the formation of the carbonated hydroxyapatite (HCA) layer, while for the Bioglass® this takes place in 6 to 8 hours, see the book by Pirhonen, E. et al. Manufacturing, Mechanical Characterization, and In vitro Performance of Bioactive Glass 13-93 Fibers. Wiley InterScience, 2005. DOI: 10.1002/jbm.b.30429 and Hench, L. L. Bioceramics: From Concept to Clinic. Journal of the American Ceramic Society, v. 74, p. 1487-1510, 1991.
Another process of fiber obtainment that has been studied is electrospinning. This technique needs the use of the sol-gel process to obtain vitreous material and, therefore, is much more expensive than the downdrawing technique, as well as being used, preferably, for obtaining submicron fibers for porous scaffolds fabrication, see Lu, H. et al. Electrospun submicron bioactive glass fibers for bone tissue scaffold. J Mater Sei: Mater Med, v. 20, p. 793-798, 2009 and Hong, Y. et al. Tissueation and Drug Delivery of Ultrathin Mesoporous Bioactive Glass Hollow Fibers. Adv. Funct. Mater, v. 20, p. 1503-1510, 2010. Thus, fiber production through the downdrawing method brings advantages such as production of continuous fibers of varied and controlled diameters and a less expensive process than the aforementioned techniques.
Regarding cellular interaction and response, a wide variety of cells may be grown over fibers or meshes, as their open structures facilitate growth of the desired organic tissue and improve the diffusion process of nutrients and excreta coming from said cells, Clupper, D. C. et al. Bioactive Evaluation of 45S5 bioactive glass fibers and Preliminary Study of Human Osteoblast Attachment. J. Mat Science: Materials in Medicine, v. 15, p. 803-808, 2004, which enables rapid healing of bone injuries and defects.
In the study of Clupper, D. C. et al. a rapid interaction was observed between bone cells (osteoblasts) and the surface of the hand-pulled fibers from glass 45S5; after fifteen minute, the cells had already adhered to the material, and their number grew over time.
Brown, R. F. et al. Growth and differentiation of osteoblastic cells on 13-93 bioactive glass fibers and scaffolds, Acta Biomaterialia, v. 4, p. 387-396, 2008 have proved that scaffolds obtained via 13-93 glass fibers have combined properties that improve deposition, bonding, differentiation and growth of osteoblasts on the biomaterial.
Moimas L. et al. Rabbit pilot study on the resorbability of three-dimensional bioactive glass fiber scaffolds, Acta Biomaterialia, v. 2, p. 191-199, 2006 verified in a preliminary study that scaffolds made of fibers obtained through melt spinning, when implanted in bone defects in rabbits, have shown full resorption capacity in 6 months and attained good results regarding repair and remodeling of the bone defect.
Regarding mechanical properties of the fibers, Clupper, D. C. et al. have demonstrated that tensile strength of 45S5 glass fibers, with average diameter of 79 μm, was of 340±140 MPa, which corroborates with other studies, such as Diego L. et al., Tensile Properties of Bioactive Fibers for Tissue Engineering Applications. J. Biomed. Mater. Res., v. 53, p. 199, 2000, which showed a 200 and 150 MPa tensile strength for 45S5 fibers of 200 and 300 μm, respectively. These studies show that fiber mechanical properties is correspondent to its diameter and, thus, the thinner the fiber, the more resistant it will be.
In this way, the use of vitreous formulations which combine properties such as: a rapid interaction with body fluids, that is, a high bioactivity, and higher glass stability, with a broad working range, enable obtaining fibers through the downdrawing process.
The downdrawing process is largely used for production of glass fibers in industrial scale, but for existing bioactive vitreous compositions up to now, this type of processing is not feasible, since they have low glass stability and normally a highly uncontrolled crystallization generating the degradation of its mechanical and bioactive properties, which in turn leads to quick rupture of the fibers, affecting or even hindering the fabrication of continuous fibers.
Therefore, for the manufacture of bioactive fibers, currently more expensive and complex processes are needed, such as melt spinning, electrospinning and laser spinning. Although, these processes only yield small fiber pieces, that is, these are not continuous fibers such as the ones obtained through downdrawing.
The lack of perspective and the high cost associated to these other techniques restrict the clinical utilization of these powdered or particulate biomaterials, thus the development of a new vitreous formulation, which enables manufacturing of continuous fibers and, subsequently, highly bioactive meshes and fabrics is distinctly innovative.
On the other hand, the compositions developed so far only allow manufacturing of devices, which do not need late thermal treatment, since the thermal energy generated on these processes is enough for rearrangement of the atoms of the glass into crystals; therefore, the industry of bioactive glasses is restricted to manufacturing powders and granulates.
The patent literature also presents documents pertinent to the study of bioactive glasses.
Thus, U.S. Pat. No. 6,517,857B2 describes a bioactive glass fiber mesh obtained from two distinct vitreous compositions, one with higher bioactivity and the other with less bioactivity. The main composition range informed is of 6 wt % of Na2O, 12 wt % of K2O, 5 wt % of MgO, 20 wt % of CaO, 4 wt % of P2O5 and 53 wt % of SiO2 for the most bioactive vitreous composition, and 6 wt % of Na2O, 12 wt % of K2O, 5 wt % of MgO, 5 wt % of CaO, 4 wt % of P2O5 and 58 wt % of SiO2 for the least bioactive composition.
The general composition of the U.S. Pat. No. 6,517,857B2 is provided on the table below:
TABLEElementwt %SiO253-60 Na2O0-34K2O1-20MgO0-5 CaO5-25B2O30-4 P2O50.5-6  
Subsequently, the fibers obtained undergo a surface treatment to increase reactivity. In this patent, the method used for obtaining these bioactive fibers is not specified, it is simply mentioned that the fibers were obtained per se. The tissue obtained has non-woven fibers, with smaller or larger pieces of fiber undergoing a spraying process in order to form the mesh while the fibers in this mesh have different diameters.
On this application, however, there is only one highly bioactive vitreous composition—which differs from the compositions used in the aforementioned patent—and because of this feature, it does not need any surface treatment to increase reactivity, which shortens processing steps, reducing costs and manufacturing time. The method used in this study to obtain bioactive fibers, the downdrawing, is the least expensive and the easiest processing method, thus leading to easy manufacturing of the present highly bioactive vitreous fabric.
Other differences are included in the composition, as shall be demonstrated in the present report.
The fiber obtained by the method used in the present application is continuous, not in pieces, ranging from millimeters to kilometers of extension, which eliminates the need, therefore, of using another technique to make the meshes and fabrics (as the spraying method in the aforementioned patent). The downdrawing machine enables the production of a non-woven fabric with or without orientation of the fibers and controlled porosity. The diameter of the fibers may also be the previously determined, allowing the choice of a single fixed diameter for the whole fabric or different fiber diameters.
U.S. Pat. No. 6,743,513B2 relates to the usage of bioactive glass and polymer layers for mechanical reinforcement of ductile metallic materials.
The published Brazilian patent document BR0605628A relates to the production of a hard, porous and bioactive ceramic matrix composed of alumina, hydroxylapatite and bioglass.
The published Brazilian patent document BR0900608A2 relates to the utilization of generic bioglass, with the same composition of the 45S5, and its crystallized version, using NaPO3 as the exclusive source of phosphor, therefore, different from the object of this application.
The published Brazilian patent document BR0711988-7 relates to a vitreous composition for implant coating.
The international publication WO1995014127A1 discloses a composite that features bioactive glass fiber in its composition or ceramic fibers interspersed with structural fibers as carbon fibers in a polymeric matrix. This composite is applied in the coating of orthopedic implants. The composition of bioactive glass fibers is different from the composition object of this application, as well as the method to obtain the fibers (spinning) and their application.
And international publication WO1996021628A1 relates to a bioactive glass with the same range disclosed by U.S. Pat. No. 6,517,857B2, that is: SiO2 53-60 wt %; Na2O 0-34 wt %; K2O 1-20 wt %; MgO 0-5 wt %; CaO 5-25 wt %; B2O3 0-4 wt %; P2O5 0.5-6 wt %, therefore, different in composition and application regarding the research object of the Applicant that led to the present application.